Treatment phase stratified outcomes of core binding factor acute myeloid leukemia.
Authors: Juhi Gor, Ian Michael Bouligny, Graeme Murray, Tilak Patel, Michael Doyel, Josh Boron, Valerie Tran, Yiwei Hang, Thuy Ho, Kyle Zacholski, Chad Michael Venn, Yanal Mufeed Alnimer, Nolan Wages, Steven Grant, Keri Renee Maher
Journal: Journal of Clinical Oncology (2023)

e19055 Background: Mutations in core binding factor (CBF) are associated with a favorable prognosis in acute myeloid leukemia (AML). However, between 30-40% of patients with CBF-AML relapse, and relative outcomes with each subsequent line of therapy remain unclear. Additionally, the overall survival of CBF-AML compared to other favorable risk molecular aberrations — such as NPM1 mut and CEBPA — is unknown in light of the addition of monoallelic CEBPA in ELN 2022. Therefore, the purpose of this study was to clarify the outcomes of CBF-AML relative to other favorable risk aberrations and to determine the relative overall survival associated with each subsequent relapse. Methods: We retrospectively analyzed 46 consecutive patients with CBF-AML treated from January 2013 to January 2022 at VCU Massey Cancer Center that underwent intensive chemotherapy (IC) with or without gemtuzumab ozogamicin. During the same study period, we analyzed a comparison cohort of 272 consecutive patients: 103 ELN 2017 intermediate-risk patients, 111 adverse-risk patients, eight patients with mono- or biallelic mutations in CEBPA, and 50 with ELN 2017 favorable-risk NPM1 mut . All patients were treated with front-line IC. We analyzed survival by the Kaplan-Meier method and compared groups with the log-rank test. Results: We analyzed 46 patients with CBF-AML across 136 treatment phases. Patients with CBF-AML had superior overall survival compared to patients with NPM1 mut (median overall survival not reached at a median follow-up time of 5.0 years versus 21.0 m., p = 0.028). There were no differences in survival between CBF-AML and AML with monoallelic or biallelic mutations in CEBPA at a median follow-up time of 3.7 years (not reached, p = 0.976). Expectedly, the overall survival for CBF-AML was superior to ELN 2017 intermediate (30.1 m., p = 0.011) and adverse (10.9 m., p &lt; 0.0001) risk disease. Next, we analyzed survival trends in the relapsed or refractory setting for CBF-AML by lines of therapy, using ELN 2017 intermediate and adverse risk cohorts as a comparison. During the first relapse, CBF-AML was associated with a significantly superior overall survival compared to the adverse cohort (19.1 m. versus 10.0 m., p = 0.024) but not the intermediate cohort (14.5 m., p = 0.734). The absence of KIT mut was not associated with improved survival compared to the ELN 2017 intermediate category at the first relapse ( p = 0.610). At the second relapse, the survival disparity disappeared between the CBF-AML and adverse risk groups (7.7 m. vs 4.0 m., p = 0.964). Conclusions: CBF-AML was associated with similar survival to mono- or biallelic mutations in CEBPA, and significantly prolonged overall survival compared to NPM1 mut . Relative to a matched cohort of adverse-risk AML at the time of the first relapse, outcomes of relapsed CBF-AML remain favorable. The relative overall survival benefit of CBF-AML disappeared at the time of the second relapse.